Approved immunotherapeutic agents (for breast cancer)

Currently, two immunotherapeutic agents are approved for the treatment of breast cancer: trastuzumab (Herceptin, Genentech) and pertuzumab (Perjeta, Genentech).

Trastuzumab is a monoclonal antibody that targets HER-2, a receptor tyrosine kinase that is overexpressed in certain cancers, notably breast cancer, though HER-2 may also be expressed by other cancers, including adenocarcinomas of the ovary, stomach and lung.

Trastuzumab received FDA approval in 1998 for the treatment of advanced HER-2–positive breast cancer; in 2006, it was approved for use as adjuvant therapy for early stage HER-2–positive breast cancer with axillary lymph node involvement.

Ado-trastuzumab emtansine (Kadcyla, Genentech) is an antibody-drug conjugate consisting of an anti–HER-2 monoclonal antibody (trastuzumab) linked to a chemotherapeutic agent (emtansine); it received FDA approval in 2013 for the treatment of HER-2–positive metastatic breast cancer in patients who have already been treated with trastuzumab and chemotherapy.

Pertuzumab is a monoclonal antibody that interferes with HER-2 signaling pathways. It was approved in 2012 for use in combination with trastuzumab for the treatment of HER-2–positive metastatic breast cancer in patients who have not been treated with other metastatic disease protocols, and as neoadjuvant (presurgical) therapy for patients with locally advanced, high-risk HER-2–positive breast cancer.

Breast cancer combination therapy/treatment algorithms

For patients with HER-2–positive metastatic breast cancer, the NCI recommends:

Doxorubicin and cyclophosphamide or paclitaxel with trastuzumab;

Single-agent chemotherapy with trastuzumab; or

Docetaxel, trastuzumab, and pertuzumab.

Trastuzumab emtansine is also an option for the treatment of metastatic or recurrent HER-2–positive breast cancer.

Current clinical trials for breast cancer

Glembatumumab vedotin, a monoclonal antibody-drug conjugate, is in development for the treatment of locally advanced breast cancer that is negative for hormone receptors (estrogen and progesterone) and HER-2 (so-called “triple negative” breast cancer). The agent combines a chemotherapeutic drug (vedotin) with a monoclonal antibody (glembatumumab) targeting the transmembrane glycoprotein NMB, which is a cell surface protein expressed by some breast cancers.

There are multiple ongoing trials in all phases investigating use of the checkpoint inhibitors pembrolizumab (Keytruda, Merck), nivolumab (Opdivo, Bristol-Myers Squibb) and atezolizumab (Tecentriq, Genentech) for the treatment of breast cancer.

Other agents in development include several dendritic cell and peptide- or vector-based vaccines, as well as an anti–HER-2 monoclonal antibody called margetuximab.